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Concept: Staphylococcaceae

244

The emergence of meticillin-resistant Staphylococcus aureus (MRSA) that can persist in the community and replace existing hospital-adapted lineages of MRSA means that it is necessary to understand transmission dynamics in terms of hospitals and the community as one entity. We assessed the use of whole-genome sequencing to enhance detection of MRSA transmission between these settings.

Concepts: Staphylococcus aureus, Staphylococcus, Methicillin-resistant Staphylococcus aureus, Staphylococcaceae

167

Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance of cellular immunity has been shown in mice, T cell responses in humans have not been characterised. Using a murine model of recurrent S. aureus peritonitis, we demonstrated that prior exposure to S. aureus enhanced IFNγ responses upon subsequent infection, while adoptive transfer of S. aureus antigen-specific Th1 cells was protective in naïve mice. Translating these findings, we found that S. aureus antigen-specific Th1 cells were also significantly expanded during human S. aureus bloodstream infection (BSI). These Th1 cells were CD45RO+, indicative of a memory phenotype. Thus, exposure to S. aureus induces memory Th1 cells in mice and humans, identifying Th1 cells as potential S. aureus vaccine targets. Consequently, we developed a model vaccine comprising staphylococcal clumping factor A, which we demonstrate to be an effective human T cell antigen, combined with the Th1-driving adjuvant CpG. This novel Th1-inducing vaccine conferred significant protection during S. aureus infection in mice. This study notably advances our understanding of S. aureus cellular immunity, and demonstrates for the first time that a correlate of S. aureus protective immunity identified in mice may be relevant in humans.

Concepts: Immune system, Gene, Human, Bacteria, Staphylococcus aureus, Staphylococcus, Coagulase, Staphylococcaceae

155

USA300 is a pandemic clonal lineage of hypervirulent, community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA) with specific molecular characteristics. Despite its high clinical relevance, the evolutionary origin of USA300 remained unclear. We used comparative genomics of 224 temporal and spatial diverse S. aureus isolates of multilocus sequence type (ST) 8 to reconstruct the molecular evolution and global dissemination of ST8, including USA300. Analyses of core SNP diversity and accessory genome variations showed that the ancestor of all ST8 S. aureus most likely emerged in Central Europe in the mid-19th century. From here, ST8 was exported to North America in the early 20th century and progressively acquired the USA300 characteristics Panton-Valentine leukocidin (PVL), SCCmec IVa, the arginine catabolic mobile element (ACME), and a specific mutation in capsular polysaccharide gene cap5E Although the PVL-encoding phage ϕSa2USA was introduced into the ST8 background only once, various SCCmec types were introduced to ST8 at different times and places. Starting from North America, USA300 spread globally, including Africa. African USA300 isolates have aberrant spa-types (t112, t121) and form a monophyletic group within the clade of North American USA300. Large parts of ST8 methicillin-susceptible S. aureus (MSSA) isolated in Africa represent a symplesiomorphic group of ST8 (i.e., a group representing the characteristics of the ancestor), which are rarely found in other world regions. Isolates previously discussed as USA300 ancestors, including USA500 and a “historic” CA-MRSA from Western Australia, were shown to be only distantly related to recent USA300 clones.

Concepts: Staphylococcus aureus, Antibiotic resistance, Methicillin-resistant Staphylococcus aureus, Vancomycin, Panton-Valentine leukocidin, Staphylococcaceae, Oxacillin, ST8:USA300

129

The purpose of the current work was to study the pattern and dynamics of biofilm formation in clinical isolates of Staphylococcus aureus and S. epidermidis in the presence of 10 antibiotics with different action mechanisms.

Concepts: Bacteria, Staphylococcus aureus, Staphylococcus, Biofilm, Design, The Current, Staphylococcus epidermidis, Staphylococcaceae

125

The vast majority of systemic bacterial infections are caused by facultative, often antibiotic-resistant, pathogens colonizing human body surfaces. Nasal carriage of Staphylococcus aureus predisposes to invasive infection, but the mechanisms that permit or interfere with pathogen colonization are largely unknown. Whereas soil microbes are known to compete by production of antibiotics, such processes have rarely been reported for human microbiota. We show that nasal Staphylococcus lugdunensis strains produce lugdunin, a novel thiazolidine-containing cyclic peptide antibiotic that prohibits colonization by S. aureus, and a rare example of a non-ribosomally synthesized bioactive compound from human-associated bacteria. Lugdunin is bactericidal against major pathogens, effective in animal models, and not prone to causing development of resistance in S. aureus. Notably, human nasal colonization by S. lugdunensis was associated with a significantly reduced S. aureus carriage rate, suggesting that lugdunin or lugdunin-producing commensal bacteria could be valuable for preventing staphylococcal infections. Moreover, human microbiota should be considered as a source for new antibiotics.

Concepts: Bacteria, Gut flora, Microbiology, Staphylococcus aureus, Antibiotic resistance, Staphylococcus, Staphylococcaceae, Staphylococcus lugdunensis

38

The microbiome can promote or disrupt human health by influencing both adaptive and innate immune functions. We tested whether bacteria that normally reside on human skin participate in host defense by killing Staphylococcus aureus, a pathogen commonly found in patients with atopic dermatitis (AD) and an important factor that exacerbates this disease. High-throughput screening for antimicrobial activity against S. aureus was performed on isolates of coagulase-negative Staphylococcus (CoNS) collected from the skin of healthy and AD subjects. CoNS strains with antimicrobial activity were common on the normal population but rare on AD subjects. A low frequency of strains with antimicrobial activity correlated with colonization by S. aureus The antimicrobial activity was identified as previously unknown antimicrobial peptides (AMPs) produced by CoNS species including Staphylococcus epidermidis and Staphylococcus hominis These AMPs were strain-specific, highly potent, selectively killed S. aureus, and synergized with the human AMP LL-37. Application of these CoNS strains to mice confirmed their defense function in vivo relative to application of nonactive strains. Strikingly, reintroduction of antimicrobial CoNS strains to human subjects with AD decreased colonization by S. aureus These findings show how commensal skin bacteria protect against pathogens and demonstrate how dysbiosis of the skin microbiome can lead to disease.

Concepts: Immune system, Microbiology, Staphylococcus aureus, Staphylococcus, Skin, Staphylococcus epidermidis, Staphylococcus hominis, Staphylococcaceae

34

 Emerging livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) persist in livestock populations and represent a reservoir for transmission to humans. Understanding the routes of introduction and further transmission is crucial to control this threat to human health.

Concepts: Health, Human, Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus, Staphylococcaceae

34

It is unknown whether healthcare workers' facial hair harbours nosocomial pathogens. We compared facial bacterial colonization rates among 408 male healthcare workers with and without facial hair. Workers with facial hair were less likely to be colonized with Staphylococcus aureus (41.2% vs 52.6%, P = 0.02) and meticillin-resistant coagulase-negative staphylococci (2.0% vs 7.0%, P = 0.01). Colonization rates with Gram-negative organisms were low for all healthcare workers, and Gram-negative colonization rates did not differ by facial hair type. Overall, colonization is similar in male healthcare workers with and without facial hair; however, certain bacterial species were more prevalent in workers without facial hair.

Concepts: Bacteria, Microbiology, Pneumonia, Nosocomial infection, Staphylococcus aureus, Staphylococcus, Coagulase, Staphylococcaceae

30

One of the most controversial concepts in health care epidemiology during the past decade has been the active detection and isolation of patients with methicillin-resistant Staphylococcus aureus (MRSA) colonization. The basic strategy is to screen inpatients for MRSA, typically with a polymerase-chain-reaction-based technology, in order to rapidly identify patients colonized with the organism and then initiate contact precautions (place them in a private room and require gowns and gloves on room entry). This approach has been used for decades to control outbreaks caused by epidemiologically important pathogens. As MRSA became endemic in hospitals, studies began to appear suggesting that active . . .

Concepts: Health care, Pneumonia, Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus, Staphylococcaceae

29

IMPORTANCE Estimating the US burden of methicillin-resistant Staphylococcus aureus (MRSA) infections is important for planning and tracking success of prevention strategies. OBJECTIVE To describe updated national estimates and characteristics of health care- and community-associated invasive methicillin-resistant Staphylococcus aureus (MRSA) infections in 2011. DESIGN, SETTING, AND PARTICIPANTS Active laboratory-based case finding identified MRSA cultures in 9 US metropolitan areas from 2005 through 2011. Invasive infections (MRSA cultured from normally sterile body sites) were classified as health care-associated community-onset (HACO) infections (cultured ≤3 days after admission and/or prior year dialysis, hospitalization, surgery, long-term care residence, or central vascular catheter presence ≤2 days before culture); hospital-onset infections (cultured >3 days after admission); or community-associated infections if no other criteria were met. National estimates were adjusted using US census and US Renal Data System data. MAIN OUTCOMES AND MEASURES National estimates of invasive HACO, hospital-onset, and community-associated MRSA infections using US census and US Renal Data System data as the denominator. RESULTS An estimated 80 461 (95% CI, 69 515-93 914) invasive MRSA infections occurred nationally in 2011. Of these, 48 353 (95% CI, 40 195-58 642) were HACO infections; 14 156 (95% CI, 10 096-20 440) were hospital-onset infections; and 16 560 (95% CI, 12 806-21 811) were community-associated infections. Since 2005, adjusted national estimated incidence rates decreased among HACO infections by 27.7% and hospital-onset infections decreased by 54.2%; community-associated infections decreased by only 5.0%. Among recently hospitalized community-onset (nondialysis) infections, 64% occurred 3 months or less after discharge, and 32% of these were admitted from long-term care facilities. CONCLUSIONS AND RELEVANCE An estimated 30 800 fewer invasive MRSA infections occurred in the United States in 2011 compared with 2005; in 2011 fewer infections occurred among patients during hospitalization than among persons in the community without recent health care exposures. Effective strategies for preventing infections outside acute care settings will have the greatest impact on further reducing invasive MRSA infections nationally.

Concepts: Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus, Staphylococcaceae